This is an application for a K24 Mid-Career Investigator Award in Patient Oriented Research for Scott H. Kollins, Ph.D. Dr. Kollins is an established expert in the areas of Attention Deficit Hyperactivity Disorder (ADHD) and stimulant psychopharmacology. He has been involved with and published a number of studies on clinical trials with ADHD patients and has conducted seminal work on the abuse potential of stimulant drugs as they pertain to the treatment of ADHD. More recently, Dr. Kollins' work has begun to identify important mechanisms that underlie the relationship between ADHD and nicotine dependence. The purpose of this K24 application is three-fold: 1) to extend Dr. Kollins' established record of patient-oriented research with individuals with ADHD; 2) to explore the genetic and neuropsychopharmacological basis of nicotine dependence in these individuals; and 3) to allow Dr. Kollins to develop more formal mentoring arrangements with post-doctoral trainees and junior faculty in the areas of ADHD and nicotine dependence. The career development plan for this application will extend the applicant's knowledge and skills in two key areas: 1) molecular genetics; and 2) functional brain neuroimaging. Dr. Kollins will leverage existing collaborative relationships at Duke University Medical Center to accomplish these aims. The research plan for this application will build on existing and pending projects to further understand the association between ADHD and nicotine dependence. These studies include: 1) an existing human laboratory study of the abuse liability of methylphenidate in adults with and without ADHD (R01DA017196); 2) an existing candidate gene study of persistent ADHD (R01NS049067); and 3) an existing laboratory study of the effects of nicotine withdrawal in ADHD and non-ADHD smokers (R21DA020806). New research will also be conducted to study the effects of stimulant drugs on smoking behavior in patients with ADHD and to explore the genetic and functional brain correlates of these effects. This research is of considerable public health significance. ADHD affects millions of individuals in the US and patients with ADHD smoke cigarettes at a significantly higher rate than the general population. Given that smoking is the single largest preventable cause of death and disease, understanding more about the relationship between ADHD and smoking/nicotine dependence therefore has the potential to prevent or treat a major public health and mental health problem.